1、 Core mechanism

Targeted bacterial metabolite glyoxylate

Drug resistant bacteria upregulate the expression of glyoxylate in nutrient deficient environments, which reshapes host epigenetic features, weakens immune responses, and helps bacteria survive under antibiotic pressure by inhibiting the activity of DNA demethylase (TET2) in host cells.

Vitamin C activates TET2 enzyme activity

Vitamin C, as a natural activator of TET2, can counteract the inhibitory effect of glyoxylate on host immunity, restore DNA demethylation function, and restart the immune defense system.

Disrupting the strategy of "false death" of bacteria

Acetaldehyde simultaneously activates the self-defense mechanism of bacteria, forming persisters to evade antibiotic killing. Vitamin C combined with antibiotics can break this metabolic adaptation and significantly reduce bacterial load.

2、 Experimental evidence

Animal model validation: In a mouse infection model, the combination of vitamin C and antibiotics increased survival rate by 60%, reduced bacterial load in tissues by 80%, and decreased levels of inflammatory factors by 50%.

Synergistic effect: Vitamin C enhances the interferon (IFN) signaling pathway, strengthens the immune cell's ability to clear drug-resistant bacteria, and inhibits STAT1 dephosphorylation, prolonging the anti-tumor immune response.

3、 Clinical application potential

Overcoming the dilemma of drug resistance: This strategy provides a non antibiotic dependent new therapy for drug-resistant bacterial infections such as Salmonella and Mycobacterium tuberculosis, especially for patients with recurrent infections or ineffective antibiotics.

Simplified treatment plan: Vitamin C, as a safe and low-cost nutrient, can be used in combination with existing antibiotics to reduce drug dosage and minimize side effects.

Preventive supplementation value: Adequate intake of micronutrients (such as vitamin C) may indirectly reduce the risk of drug resistance gene transmission by maintaining gut microbiota balance.

4、 Future research directions

Explore the synergistic effects and optimal dosage combinations of vitamin C with other antibiotics such as beta lactams and quinolones.

Evaluate the impact of long-term vitamin C supplementation on the evolution of drug-resistant bacterial populations.

Developing novel antibacterial drugs targeting the glyoxylic acid-TET2 axis